Adrenergic Agonists- T2 Flashcards
define asthma
increased inflammation and contractile responsiveness of bronchial smooth muscle in response to allergens, pollutants, exercise and upper respiratory infections.
4 structure examples given of beta2 adrenergic agonists
albuterol, metaproterenol, terbutaline, and formoterol.
beta2 adrenergic agonists are suppled as ____ mixtures of R and S forms of the drug
racemic
Levalbuterol is which isomer?
R
which isomer is more efficacious and why is the other not as good
R. S tends to hang around longer making it more susceptible to metabolism and has a longer half life.
beta2 adrenoceptors predominate as the primary adrenergic receptor producing __
relaxation of bronchial smooth muscle.
activation of M3–> ___ –> —
increase Ca (PLC)–> increase bronchoconstriction
activation of B2–> ___ –> ___ –> ____
increase cAMP–> PKA –> decrease Ca
is beta2 selectivity absolute?
no, if you take enough, you can activate beta1.
what size particle is optimal for bronchial tree deposition
2-5 micrometers
systemic effects of beta agonists
skeletal muscle tremors, weakness, tachycardia, CNS excitation.
genetic studies have revealed that polymorphism in ____ may modify asthmatic disease or response
beta2 receptor
polymorphism is __ and mutation is ___
polymorph: greater than 1% and mutation is less than 1%
differences in ___ lead to differences in the ___
receptors, patients response to the drug
these polymorphisms change how the receptors react-
the beta receptors couple to cAMP production though a Gs, this cAMP buildup through PKA in the bronchioles is going to cause bronchiodilation, this is going to be caused by removal of Ca, ig we have a polymorph then the receptor doesn’t couple well to the G protein system so we reduce the ability for the receptor to cause bronchodilation.
polymorphisms in what two cases cause patients to be poor responders to beta agonists? and what would you use instead
Thr164 and ile164. would want to use a muscarinic antagonists instead.
Thr164–> ile polymorphism results in
poor coupling of the receptors to adenylyl cyclase activation
Arg16–>Gly polymorphism results in
more rapid down regulation of the receptor
Gln27–>Glu polymorph shows
greater resistance to down regulation than the Arg16 receptor
Gly16_Gln27_ile164:
poor adenylyl cyclase coupling vs Thr164
Gly16_Gln27_Thr164:
rapid receptor downregulation vs Arg16
Arg16_Glu27_ile164:
resistant to receptor downregulation vs Gln27
